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Journal of Ethnopharmacology 65 (1999) 29–51
Ayahoasca: an experimental psychosis that mirrors thetransmethylation hypothesis of schizophrenia
Alicia B. Pomilio a,1,*, Arturo A. Vitale a,1, Jorge Ciprian-Ollivier b,2,3,Marcelo Cetkovich-Bakmas b,3, Raquel Gomez b,3, G. Vazquez b,3
a Programa de Plantas Toxicas y Medicinales. Metabolismo de Sustancias Sinteticas y Naturales ( PROPLAME -CONICET ) ,
Departamento de Quımica Organica, Facultad de Ciencias Exactas y Naturales, Uni 6ersidad de Buenos Aires, Pabellon 2 ,
Ciudad Uni 6ersitaria, 1428 Buenos Aires, Argentinab Departmento de Psiquiatrıa, Facultad de Ciencas Medicas, Uni 6ersidad de Buenos Aires, Centro de Psiquitrıa Biologica,
Francisco de Vittoria 2324 , 1425 Buenos Aires, Argentina
Accepted 27 February 1997
Abstract
The experimental psychosis observed after drinking Ayahoasca, a South American hallucinogenic beverage fro
the Amazon Indians, reproduces the pathologic transmethylation theory of schizophrenia. This theory postulates
decrease in the monoamine oxidase (MAO) activity, which results in the accumulation of methylated indolealklamines, such as bufotenin (5-hydroxy-N ,N -dimethyltryptamine), N ,N -dimethyltryptamine (DMT) and 5-methox
N ,N -dimethyltryptamine. These substances are strong hallucinogens as has been previously confirmed experimentally
On the other hand, it is known that Ayahoasca is a beverage usually prepared by boiling two plants, one of them ric
in i-carbolines, which are naturally occurring strong inhibitors of MAO, and the other with high quantities of DMT
This particular combination reproduces what is supposed to occur under pathologic conditions of different psychose
The effects of Ayahoasca were studied in subjects, assessing urine levels of DMT by gas chromatography-ma
spectrometry (GC-MS) before and after the intake of the beverage. The results of this study confirm that th
hallucinogenic compounds detected in the healthy subjects’ (post-Hoasca, but not before) urine samples are the sam
as those found in samples from acute psychotic unmedicated patients. The chemical composition of the Ayahoasc
beverage, and of the plant material used for its preparation are also reported as well as psychometric an
neuroendocrine subject parameters. © 1999 Elsevier Science Ireland Ltd. All rights reserved.
Keywords: Ayahoasca; Methylated indolalkylamines; Psychodisleptic; Gas chromatography-mass spectrometr
Transmethylation hypothesis; MAO; Schizophrenia
* Corresponding author. Fax: + 54 1 8143952; e-mail: proplame@qo.fcen.uba.ar1 Research Member of the National Research Council of Argentina (CONICET).2 President of the World Federation of Societies of Biological Psychiatry (WFSBP; 1997).3 President of the Argentine Association of Biological Psychiatry.
0378-8741/99/$ - see front matter © 1999 Elsevier Science Ireland Ltd. All rights reserved.
PII: S0378-8741(98)00163-9
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A.B . Pomilio et al . / Journal of Ethnopharmacology 65 (1999) 29–5130
1. Introduction
Transmethylation hypothesis of schizophrenia
(Stam et al., 1969; Smythies, 1983) proposes that,due to enzymatic disturbances (Buscaıno et al.,
1966, 1969), schizophrenic patients produce high
amounts of methylated indolealkylamines, such asbufotenin (5-hydroxy-N ,N -dimethyltryptamine)
(Fuller et al., 1994), 5-methoxy-N ,N -dimethyl-
tryptamine and N ,N -dimethyltryptamine (DMT)(Friedhoff and Van Winkle, 1964; Fischer et al.,
1971; Ciprian-Ollivier et al., 1986), which are
strong hallucinogenic compounds for healthy sub- jects. These substances are preferential substrates
for monoamine oxidase (MAO), in a way that
when a high single dose is given, 30 min later only1% can be recovered from blood and/or urine
samples (Hryhorczuk et al., 1986; Sitaram and
McLeod, 1990). In spite of this high turn-over,
methylated indolealkylamines have been reportedin urine samples from psychiatric patients, not
only schizophrenics (Tanimukai et al., 1970;Saavedra and Axelrod, 1972; Strahilevitz et al.,
1975). In our previous work (Ciprian-Ollivier et
al., 1986, 1988; Ciprian-Ollivier, 1991), in agree-ment with other authors (Rodnight et al., 1978;
Murray et al., 1979; Checkley et al., 1980), it has
been proposed that these compounds are relatedto perceptual disturbances, remarking that not
only true hallucinations but more subtle percep-
tual disturbances are present in several entities.Therefore, methylated indolealkylamines may
play the role of ‘state markers’ for clinical orsubclinical psychoses rather than being a trait of
any diagnostic category. Their accumulation in
patients could be caused either by an accelerationin the kinetics of their production or, and most
probably, by a decrease in the kinetics of the
enzyme (MAO) responsible for the breakdown of the methylated indolealkylamines (Mc Geer et al.,
1978; Raisanen and Karkkainen, 1978, 1979).
Many reports are known of decreased MAO ac-
tivity in schizophrenia, which are thus in agree-ment with this theory (Davis et al., 1982).
Decreased MAO activity allows the accumulationof indolealkylamines, crossing the blood brain
barrier (BBB) and acting on the central nervous
system (CNS), due to the fact that these com-pounds are not necessarily produced within CNS.
In the South American Amazon Basin a hallu
cinogenic beverage is used by shamans to induc
mystic states that clearly mirrors this situatio
Ayahoasca or Hoasca tea (the Brazilian name fo
Ayahuasca; see Section 1.1) is essentially made b
boiling two plants, Banisteriopsis caapi and Psy
chotria 6iridis. The first is rich in i-carboline
derivatives, which are strong natural MAO inhibitors, and the second contains high amounts o
DMT, being an important natural source of th
compound (Rivier and Lindgren, 1972; McKenn
et al., 1984; McKenna and Towers, 198
McKenna et al., 1986). In an empirical wa
Amazon shamans discovered, many years ago
that in order to have the hallucinogenic effect o
one of the plants, Psychotria sp., the presence o
the other, B . caapi , was needed. Therefore, p
ripheral MAO inhibition by i-carbolines allow
the concentration of DMT and further BB
crossing, thus exerting their hallucinogenic effec
in the CNS.
In this paper, we studied several biological e
fects of Ayahoasca or Hoasca tea in order t
evaluate the ability of this beverage to modula
serotonergic receptors, and through these result
to determine to what extent cortisol, prolactin an
serotonin levels as well as perceptual and cogn
tive processes are affected. As is known, recen
basic research with radioligands showed outstand
ing differences in the anatomical distribution o
the 5-HT receptors in rat and human brain, antherefore, human research is necessary as a
ethnopharmacological contribution to the effec
due to Hoasca intake. Furthermore, the occu
rence of DMT in Ayahoasca or Hoasca tea and i
the urine samples from the subjects confirm tha
the reported biological and cognitive effects a
produced by these methylated indolealkylamin
assisted by the i-carboline derivatives.
1.1. Ethnobotany of Ayahoasca
South American psychoactive drinks and snuf
used by the indian tribes for shamanic, medicin
and/or religious ceremonial purposes have bee
extensively reviewed and studied by ethnobotan
cal explorers, botanists, chemists, anthropologis
and pharmacologists (Schultes, 1954, 1957, 196
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A.B . Pomilio et al . / Journal of Ethnopharmacology 65 (1999) 29–51
Rıos, 1962; Biocca et al., 1964; Marini-Bettolo et
al., 1964; Efron et al., 1967; Schultes et al., 1969;
Flores and Lewis, 1978; Schultes, 1985). Further-
more, a variety of other plants and fungi contain-
ing hallucinogenic substances has been used as
constituents of medicinal, ritual and recreational
drinks and snuffs, also in relation to religious
practices in ancient and contemporary aboriginalSouth American groups (Schultes, 1967a,b,
1969a,b, 1972; Lewis and Elvin-Lewis, 1977;
Schultes, 1977; Schultes and Hofmann, 1980).
The first european references of the Ayahoasca
beverage or Ayahuasca drink (aya-huasca, means
dead man’s vine, vine of the dead or vine of the
souls, in quechua, the language of the ancient
Incan Empire) are due to missionary jesuits, thus
Pablo Maroni in 1737 described it as a narcotic
drink, and Magnin (1740) its use as a medicinal
plant by the Maynas Indians, thus suggesting that
the same name was used for both the drink and
the plant. Primitive cultures considered the vessels
for drinking Ayahuasca or other psychedelic
drinks as sacred, and consequently, artistic
coloured objects were designed with mythological
figures or subjects, or sacred animals, which are
carefully kept in Ethnographical Museums of
Peru, Ecuador, Colombia and other countries
with a rich precolumbian culture. Therefore,
through archeological research it is possible to
follow the precolumbian evolution of the sacred
plants in the different ecological systems of thisregion, as well as the folk-preparation, ritual con-
sumption and erotic effects. Thus, collective cere-
monies used large bowls, from which each
member swallowed the ritual liqueur in turn. In
contrast, in healing ceremonies or cure rituals
only the shaman or tribe medicine-man in a spe-
cial house drank the sacred brew in a small pot
(Naranjo, 1986). Antique ceramics of these small
vessels come from the Sangay stage (2400 b.c.) in
Ecuador (Naranjo, 1986). A variety of metallic
cooking pottery, particularly the so-called ‘ollasde brujo’ for making the Ayahuasca potion, was
also found in the littoral region of Ecuador from
the evolved Milagro-Quevedo culture (500 – 1500
a.c.) with a sophisticated agriculture and metallur-
gical knowledge including the use of gold and
copper. Two ethnical groups, the Colorados and
the Cayapas, who live in this region, maintain th
shaman use of the Ayahuasca extract under th
name ‘pinde’ or ‘pilde’, and ‘nepi’, respective
(Naranjo, 1986).
In postcolumbian times the mestizo population
continued the ritual and ethnomedicinal uses o
the Ayahuasca potions, but unfortunately som
reports of explorers and investigators were somewhat confused, probably due to the different abo
riginal names in the tribal languages given to th
potions, plants and admixtures. In addition, eac
tribe has its own name for the same plant. Fo
example, in Ecuador, Ayahuasca is known a
‘yaje’ in the north, ‘mii’ for the Aucas an
‘natema’ for the Shuar (Naranjo, 1979). Richar
Spruce, who lived closely with the native Amazo
nian people, gave detailed, amusing and pione
information in english on the malpighiaceous na
cotic, first described the caapi liana, now called B
caapi (Spr. ex Griseb.) Morton (Malpighiaceae
and witnessed its use among the Tukanoan Ind
ans of the Vaupes river of Brazil in 185
(Schultes, 1968; Pinkley, 1969).
The forest liana B . caapi grows spontaneous
in an extensive area of the Orinoco and Amazo
Basin, including Venezuela, Colombia, Ecuado
Peru, Bolivia, and Brazil, in the rain forest an
jungle, with high humidity. In the littoral regio
of Ecuador there is another area of Ayahuasc
western Quito, on the other side of the And
mountains (Naranjo, 1979).Even though the amazonian Ayahuasca beve
age occasionally contains only the bark of th
jungle liana B . caapi or Banisteriopsis inebrian
(Malpighiaceae), which contain i-carbolines,
is often a complex narcotic due to the additio
of other plants (admixture or mixture, ‘ch
cruna’ in quechua) (Schultes, 1972). Del Castill
(1962) described the chacruna as Psychotria spp
(Rubiaceae). However, Borman, a missionar
linguist reported that both the malpighiaceou
Banisteriopsis rusbyana (now known aDiplopterys cabrerana) and the rubiaceou
Psychotria psychotriaefolia (Seem.) Standl., a rela
tive of P. 6iridis, were added to the ‘yaje’ drin
prepared from B . caapi in order to increase an
intensify the visions (Schultes, 1969b). Oth
Psychotria spp. from northwestern Amazon wer
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A.B . Pomilio et al . / Journal of Ethnopharmacology 65 (1999) 29–5132
detailed by Schultes (1985). Maximum hallucino-
genic effect is obtained with leaves of Psychotria
carthagenensis Jacq., P. 6iridis Ruiz et Pavon (Ru-
biaceae), or the malpighiaceous jungle liana D.
cabrerana (Cuatrecasas) Gates (formerly known
as B . rusbyana) (Gates, 1979, 1982), all of which
contain as major component DMT. P. carthage-
nensis is also a Maya medicinal plant againsttoothache (Arnason et al., 1980). Amazon Kofan
Indians of eastern Ecuador and Colombia used
Banisteriopsis and small rubiaceous fruits from
the plant called ‘o-pri-to’, the same name by
which they refer to the ‘heavenly people’ with
whom they commune during the ‘yaje’ intoxica-
tion (Pinkley, 1969). The Cashinahua call the
admixture ‘kawa’, while the Culina Peruvian Indi-
ans ‘appane’, and the Sharanahua Indians, lin-
guistically related to the Cashinahuas, also called
the plant ’kawa’. These tribes of the Purus river in
Loreto, Peru also recognized, like the
Cashinahua, different kinds of this rubiaceous
additive (Rivier and Lindgren, 1972; Ruf, 1972).
The collection of admixtures with voucher speci-
mens and the aboriginal name, obtained by Rivier
and Ruf from these two ethnic groups on the
Purus river is the largest from a specific group of
indians (Pinkley, 1969; Rivier and Lindgren, 1972;
Ruf, 1972).
Other occasional additives used particularly in
Peruvian Amazon include leaves from Apocy-
naceae (Tabernaemontana spp.), Solanaceae,Acanthaceae, and many others such as cacti,
mints, sedges, and ferns (Schultes, 1969b, 1972,
1985; Pinkley, 1969; Rivier and Lindgren, 1972;
McKenna et al., 1984; McKenna and Towers,
1985; McKenna et al., 1986). The solanaceous
genera include Nicotiana sp., Brugmansia sp. and
Brunfelsia sp., which contain alkaloids, such as
nicotine, scopolamine, and atropine, which addi-
tionally affect both central and peripheral adren-
ergic and cholinergic neurotransmission. The
admixture selected depends on the magical, medi-cal or ritual use, e.g. Toe negra in Amazonian
Peru (Teliostachya lanceolata var. crispa, family
Acanthaceae), is cultivated for use alone as a
narcotic and as an additive to Ayahuasca (B .
caapi ). When used alone the boiling of ten leaves
for 7 h results in the loss of sight for 3 days,
during which time conversation with the spirit o
the plant is possible. The plant Juanulloa ochrace
(Solanaceae), which contains the alkaloid pa
quina is called Ayahuasca in the Colombian Putu
mayo, and is added to Banisteriopsis drinks. Als
the Colombian Vaupes, use Sabicea amazonens
(Rubiaceae) leaves to make the drink sweet in
stead of bitter.One investigator of medical practices among
the Siona Indians of the Colombian Putumay
who are known as having a rich ethnopharmaco
poea, reported that these natives recognize 1
different classes of yaje and that each of thes
admixtures gives a different kind of visio
(Rocha, 1905; Schultes, 1968; Reichel-Dolmatof
1970; Schultes, 1972). Also the Barasana Indian
of the Piraparana river of Colombia know 2
varieties. Some of these names may be alternat
names for the same plant, others may represen
age or ecological forms of B . caapi , but som
undoubtedly refer to different plants that are use
as admixtures.
Several tribes of the Peruvian Amazon use
Ayahuasca for healing, ritual aspects being mor
strongly marked in tribal usage (Delgado et a
1972) in other regions where its use is more wide
for magic objectives, as in the Ecuadorian Ama
zon (Villavicencio, 1858), where the sundry tribe
of the upper Napo river use Ayahuasca for so
cery, witchcraft, prophecy and divination. Mor
over, ethnic groups of south and middle Ecuadouse the drug as a concentrated extract, while th
Tucanos from Colombia use a diluted extract.
Therefore, the drug practice dates to precolum
bian times, and a short time after the Spanis
conquest, Ayahuasca was integrated into the eth
nomedical traditions of the mixed population
(european plus aborigines) called mestizos. Nowa
days the drug is important in ethnomedicine an
shamanism in indigenous mestizo populations o
the Amazonian region for healing, for divinatio
and as a magical tool for the supernatural realm(Dobkin de Rıos, 1970, 1972; Luna, 1984). A
though little is known of the medicinal propertie
of the hallucinogenic plants, reports by Schulte
and other ethnobotanists who have participate
in the drinking of the hallucinogenic potion
suggest that a variety of physiological effects ac
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A.B . Pomilio et al . / Journal of Ethnopharmacology 65 (1999) 29–51
companied the hallucinogenic experience, the
most common being vomiting and diarrhea. Dur-
ing native ceremonies, repeated references are also
made to the cleansing (emesis) and purifying
properties of these drugs. Since parasitic
helminthic and protozoal infestations of the gas-
trointestinal tract are prevalent throughout the
tropics, and especially in the Amazon basin proto-zoal diseases, such as malaria, leishmaniasis,
Chagas disease, various trypanosomiasis and tox-
oplasmosis, shamans and medicinal tribe men (he-
chiceros) select alkaloid-containing plants which
cure by expelling the parasites, e.g. hallucinogenic
isoquinoline and tryptamine-related plant alka-
loids are known as powerful emetics, and as an-
timicrobials and anthelmintics. Consequently,
Cavin developed an in vitro chemical screening
test to determine the effects of various alkaloids
against Trypanosoma cruzii (Chagas disease) epi-
mastigote forms. Harmine, quinine hydrochloride,
vinoblastine sulfate, emetine dihydrochloride and
atropine showed marked effects (over 70% inhibi-
tion after 96 h), while arecoline and berberine,
which are employed as anthelmintics, showed 40%
inhibition after 96 h (Rodrıguez et al., 1982).
Psychoactive alkaloids are effective antagonists of
the neuromuscular system of helminths, inhibit
protozoan parasites and were selected by Amazo-
nian people for their medicinal value and also
incorporated into religious ceremonies (Rodrıguez
et al., 1982). Aboriginal groups and especiallyshamans correlated the psychotropic effects of
these alkaloids and the alleviation of symptoms
caused by parasitic worms and protozoans and
thus used the former as a dosage indicator. They
incorporated these plants into religious cere-
monies using psychoactivity as an effective dose
marker (Rodrıguez et al., 1982), and included this
knowledge in the shamans’ education. The bor-
rachera yage potion prepared by the witch for
medicinal purposes is usually a dreadful-tasting,
reddish-coloured decoction as reported by Ro-drıguez et al. (1982) when drinking it with the
Kamsa Indians of the Upper Putumayo in
Colombia. After ingestion, they experienced no
hallucinogenic effect, but violent vomiting and
diarrhea. The potion was prepared from the bark
of the vine B . caapi , without any admixture.
Banisteriopsis species are not usual in Argentin
(O’Donell and Lourteig, 1943; Dawson, 196
Rossow, 1988), but one of the species found is B
nitrosiodora Griseb., which is practically devoid o
alkaloids (Deulofeu, 1967a,b). In fact, the hallu
cinogenic drink is not used in Argentina. Instead
other tryptamine-containing species of the genu
Piptadenia (Leguminosae) grow in northwesterArgentina, and were used in hallucinogenic snuf
by the Lules Indians of the western Chaco, an
also in ritual ceremonies of the Matakos Indian
(Deulofeu, 1967b). The chemical componen
were studied in our country by Iacobucci an
Ruveda (1964).
In Brazil, instead, the hallucinogenic beverag
Ayahoasca has an aboriginal as well as a cul
use.The Kachinaua tribes of Brazil prepare th
hallucinogenic drink directly from Banisteriops
taste6inii (Schultes, 1972). During Spruce’s field
work on the upper Negro river of Brazil an
adjacent Colombia and Venezuela, the Tukanoa
Indians used ‘caapi ’ (Tupi name for ‘grass’ o
‘thin leaf’ in Brazil) to obtain visual hallucination
and a feeling of bravery. Also the primativ
Guahibo Indians along the Orinoco at th
Cataracts of Maypures used ‘caapi ’ as a drink an
also chewed the dried stem. These tribes use it i
a traditional medical use, reserved for the witch
medicinal man or shaman, who takes the dru
and interprets the visions in order to detect th
cause of illness. In addition to this therapeutic usof the drug, there is also a social one in order t
have visions (Ducke, 1958; Schultes, 1985).
From Amazonian Brazil Prance (1970) reporte
the preparation and use of the drink not only b
aboriginal groups but also by the Brazilian town
men who belong to a cult centered aroun
Ayahuasca (called cipo, Ayahoasca, Hoasca te
Daime). The vine of Banisteriopsis is cut int
pieces and boiled in a saucepan of water, th
leaves of Psychotria are added at this point an
the mixture is further boiled for ca. 30 min. Thdark brown liquid is cooled and may be bottle
and corked to be consumed at home for up to
weeks. Families use the beverage without appa
ent harm or addiction and individuals used t
gather for large drinking bouts. Always there is
person who does not drink in order to preven
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A.B . Pomilio et al . / Journal of Ethnopharmacology 65 (1999) 29–5134
bad hallucinating experiences in new consumers
and to control the progression of the visions. The
members shut their eyes and wait for the visions
after drinking. Detailed experiences have been
previously reported (Prance, 1970; Lewis and
Elvin-Lewis, 1977), showing an increase of com-
munication and extrasensory perception beyond
usual conscious levels.Nowadays, several brazilian syncretic religious
movements are based on the ritual use of Aya-
hoasca, e.g. Uniao do Vegetal, that are described
in this paper.
1.2. Chemistry and mechanism of action
Harmine was detected in the material sent by
Spruce from Brazil in 1852 and analysed in 1968
(Schultes et al., 1969) and earlier (Chen and
Chen, 1939) in the stem, leaves and roots of an
authentic sample of B . caapi . Harmine, harmaline
and (+)-THH were reported from B . caapi and
Prestonia amazonicum (Hochstein and Paradies,
1957).
The chemical composition of the South Ameri-
can Banisteriopsis species was analysed in Ar-
gentina, in our Department of Organic Chemistry
by Deulofeu (1967a), who described harmala al-
kaloids. Also, Cassels from our Department de-
scribed the healing practice, botany and
chemistry from the Peruvian Ayahuasca (Delgado
et al., 1972). The psychotropic properties of thesealkaloids and the so-called harmaline syndrome
was described by Naranjo (1967), who carried
out electrophysiological studies on cats.
DMT was reported in B . rusbyana (now D.
cabrerana), harmine and harmaline in Banisteri -
opsis spp. (Der Marderosian et al., 1968; Agurell
et al., 1968a,b, 1969), as well as DMT and other
non-indole alkaloids from leaves of P. 6iridis
(Der Marderosian et al., 1970). In the same
study, another Psychotria was reported to contain
DMT only, while a third specimen of Psychotrialeaves was totally devoid of alkaloids. The indi-
ans mixed all three of these Psychotria species
with Ayahuasca, according to Pinkley (1969).
Rivier and Lindgren (1972) identified substan-
tial amounts of DMT and traces of N -methyl-
tryptamine (MMT) and 2-methyl-1,2,3,4-tetra-
hydro-i-carboline (MTHC) in the leaves of P
6iridis, and when DMT was not present, the
found instead MMT and MTHC. These author
also found that P. carthaginensis contains a large
amount of alkaloids than P. 6iridis, practically a
DMT and that other species of Psychotria (P
emetica, P. bacteriophylla and P. undulata) wer
devoid of indoles and i-carbolines. Tracamounts (0.007– 0.0001%) of another six i-ca
bolines (harmic amide, acetyl norharmine, ketot
trahydronorharmine, harmine N -oxide, harm
acid methyl ester and harmalinic acid) have bee
also reported (Hashimoto and Kawanishi, 197
1976) in addition to the three main constituen
as well as the pyrrolidine orchideaceous alkaloid
shihunine and dihydroshihunine from B . caap
(Kawanishi et al., 1982). McKenna et al. (1984
analysed the components of admixtures, the alka
loids of Ayahuasca from Peru, alkaloid conten
variations in several B . caapi cultivars and also
three admixture plants were screened for alk
loids. These authors reported that the Ayahua
queros of Peru recognized several different ‘kind
of Ayahuasca, which varied in their psychologic
effect based in part on the type of admixtu
plants, and in part on the type of B . caapi (e.
‘cielo’,‘lucero’, ‘rumi’; as many as ten kinds o
Banisteriopsis vine), probably different cultivar
races, or chemical or morphological varietie
However there were no outstanding morpholog
cal differences between the three or four kinds o
B . caapi collected, but considerable alkaloid con
tent variation between the samples. The varia
tions observed may be due to the age of th
plant, and/or environmental conditions (so
light, water) affecting each plant growt
McKenna et al. (1984) found alkaloid amoun
similar to those of Rivier and Lindgren (1972
and identified DMT as the single major ba
(1–1.6 mg/g dry wt), and sometimes only trace
of MTHC in the leaves of P. 6iridis from Peru
but no alkaloids in its fruits or stems. No alkaloids were found in the P. carthaginensis, used b
one ayahuasquero. The occurrence of tiny dolma
tia-like structures (espinas) were pointed out b
the Ayahuasqueros as the key feature to identif
good Psychotria from false chacrunas (McKenn
et al., 1984). In fact, the colleter types and th
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A.B . Pomilio et al . / Journal of Ethnopharmacology 65 (1999) 29–51
relationship to the bacterial leaf nodule symbio-
sis is very important in the systematics of Rubi-
aceae (Lersten, 1975).
D. cabrerana (the malpighiaceous admixture;
‘chagro-panga’ or ‘ocoyage’) gave DMT (1.74
mg/g dry wt) and an extremely trace amount of
5-OH-DMT by GC-MS, usual admixture in
southern Colombia and Ecuador (Pinkley, 1969).Indole oligomers, polyindoline alkaloids and
pyrrolidinoindolines, such as psycholeine,
hodgkinsine, calycanthidin, quadrigemine, psy-
chotridine, isopsychotridine, and other tetramer
and pentamer related compounds have been also
isolated from Psychotria spp. (Libot et al., 1987;
Gueritte-Voegelein et al., 1992). It is interesting
to note the outstanding accumulation of Ni in
some Psychotria species (1.8– 4.7% Ni in leaves
of P. douarrei from New Caledonian), and the
fact that P. baillonii only grows in extremely
alkaline soils (Ni-tolerant ecotypes) (Hegnauer,
1990).
Only a few chemical analyses of the narcotic
beverage have previously been carried out (Clin-
quart, 1926; Rouhier, 1926; Chen and Chen,
1939; Rivier and Lindgren, 1972; McKenna et
al., 1984). Hochstein and Paradies (1957) found
harmine, harmaline and tetrahydroharmine
(THH) in the aqueous extract used by the na-
tives and that the concentration of harmaline
and THH were greater than in the plant. Der
Marderosian et al. (1970) isolated DMT, muchharmaline and a little harmine from ‘nixipae’ of
Cashinahua (stem of Banisteriopsis sp. and the
leaves of two not completely identified species of
Psychotria).
One of the most complete studies of the
plants and drink is due to Rivier and Lindgren
(1972), who identified harmine, harmaline,
THH, harmol and 6-methoxytryptamine in B .
caapi (GC-MS) and DMT, MMT and MTHC
in P. 6iridis and P. carthagenensis (vide supra).
They also analysed the drink, called Ayahuascain Peru identifying harmine, harmaline, THH
and DMT, and quantified the alkaloids adminis-
tered in the drink. The indians distinguished
three kinds of the vine (B . caapi ): red, black
and white, based more in the colour of the
drink than on the plant morphology. The Peru-
vian mestizos made no distinction between th
red and the white drink, knowing only blac
and white. In this whole region the stems o
Banisteriopsis sp. were always blended with th
leaves of Psychotria sp.. The Sharanahua distin
guished at least two kinds of Psychotria, an
the Culina two species of Psychotria, too. Othe
plants are sometimes added to or taken togethewith the beverage, such as Opuntia sp. (Ca
taceae), Datura sp. (probably D. sua6eolens
(Solanaceae) and Nicotiana sp. (Solanaceae
Customarily, the indians smoke all night lon
when taking the Ayahuasca drink (Rivier an
Lindgren, 1972).
McKenna et al. (1984) also studie
Ayahuasca brews obtained from Ayahuasquero
of the Peruvian towns of Iquitos, Pucallpa an
Tarapoto. Harmine, harmol, harmaline an
THH were the major i-carbolines in all th
samples, while harmalol was not detected in an
sample except one. DMT was found in all th
samples in one from Tarapoto prepared with P
carthagenensis instead of P. 6iridis. The samp
from Pucallpa had the highest total alkaloi
content: 75.7 mg/g dry wt of which 76% wa
harmine, 10.6% was THH, and 7.6% was DMT
Both regions used different methods of prepara
tion. Purus: 1h-boiling, while Pucallpa ca. 10– 1
h, adding fresh water, filtering and further con
centrating.
The mechanism of action earlier suggeste(Efron et al., 1967; Schulgin, 1976) to explai
the oral hallucinogenic activity of the Ayahuasc
drink is based on the fact that the i-carboline
of B . caapi are highly active reversible inhibitor
of MAO (Udenfriend et al., 1958; McIsaac an
Estevez, 1966; Buckholtz and Boggan, 1977
and consequently prevent DMT deamination b
visceral MAO, thus transforming the potent ha
lucinogen DMT present in the Psychotria spp
into an orally active compound. In fact, DM
is known to be inactive orally (Schulgin, 197due to degradation by intestinal and hepat
MAO.
The fully aromatic i-carbolines are the mo
effective MAO inhibitors, and the activity d
creased with increasing saturation of the pip
ridine ring, tetrahydro-i-carbolines still showin
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A.B . Pomilio et al . / Journal of Ethnopharmacology 65 (1999) 29–5136
significant activity (Udenfriend et al., 1958). Ex-
periments by Fuller et al. (1970) showed that
harmaline selectively inhibited oxidation of sero-
tonin, indicating that it was a specific inhibitor of
MAO-A. However, the first empirical demonstra-
tion of the effect of Ayahuasca drink on MAO
was due to McKenna et al. (1984), who screened
in vitro various i-carbolines, mixtures of i-car-bolines and Ayahuasca drinks for activity as
MAO inhibitors, and compared structure–activity
relationships in assays using rat-liver as the source
of MAO and 5-hydroxy [side-chain-2-14C]-
tryptamine creatinine sulphate as substrate. The
degree of Ayahuasca drink MAO inhibition was
directly correlated in vitro with the concentration
of MAO-inhibiting i-carbolines. Thus, one
Ayahuasca sample (3.5 mg/ml total alkaloids) still
showed \40% inhibition of the enzyme at 10−5
full strength (I 50=1.58×10−5
M), while a sec-ond Ayahuasca sample (4.8 mg/ml total alkaloids)
exceeded 50% inhibition even at one ten-millionth
(10−7) (I 50B1.0×10−7 M) the concentration of
the undiluted brew. Inhibition experiments using
mixtures of i-carbolines further indicated that
their effects in combination are additive, rather
than synergistic or antagonistic (McKenna et al.,
1984). The I 50 (3.16×10−7 M) of an equimolar
mixture of harmine+harmaline+THH (1:1:1) is
ca. intermediate between the I 50 value of the most
active constituent of the mixture (harmaline, I 50=1.58×10−8 M) and the least active (THH, I 50=
1.77×10−6 M), thus indicating that these
compounds do not interact synergistically with
respect to their inhibition of MAO. The
Ayahuasca ‘analogue’ (69% harmine+26%
THH+4.6% harmaline, with a similar composi-
tion to one of the Ayahuasca samples) showed I 50values nearly identical with those of the equimolar
mixture (3.98×10−7 M and 3.16×10−7 M, re-
spectively) indicating that the combination of
harmine and THH alone can account for most of the MAO inhibition exhibited by Ayahuasca. Al-
though harmaline is equivalent to or slightly
stronger than harmine as MAO inhibitor, none or
only traces in Ayahuasca are required because it
does not contribute significantly to the MAO
inhibition described (McKenna et al., 1984).
2. Materials and methods
2.1. Plant material and Ayahoasca samples
The botanical material and Hoasca teas we
obtained from Brazil, ‘Uniao do Vegetal’ (UDV
(‘Santo Daime’) with the consent of the Presiden
of the Scientific Studies Society.The plant material consisted of two differen
species used for the preparation of the hallucino
genic beverage: the stems of B . caapi (Spruce e
Griseb.) Morton (Malpighiaceae) and the leav
of P. 6iridis Ruiz et Pavon (Rubiaceae). It wa
dried at room temperature in the air withou
exposure to the sun to prevent any photochemic
degradation and/or transformation. Moreove
according to the ayahuasqueros sun exposure ma
destroy the effects of the tea.
Voucher specimens of B . caapi and P. 6irid
were deposited in the Herbarium of the Laborato
rio de Plantas Vasculares, Departamento de Cien
cias Biologicas, Facultad de Ciencias Exactas
Naturales, Universidad de Buenos Aires, an
identified by Professor Dr Ramon Palacios an
Dr Enrique M. Zallocchi.
Hoasca tea samples were carried refrigerate
from Brazil to Argentina. They were prepared b
the respective Brazilian cult-groups in the trad
tional long procedure, by boiling a mixture of B
caapi and P. 6iridis. Dark green-brownish dens
liquids were obtained.The tea samples were administered at a stan
dardized dose based on the previous experience o
usual users, ca. 100 ml.
2.2. Extraction of the alkaloids
The alkaloids were obtained separately from
the stems of the liana B . caapi and the leaves o
P. 6iridis according to the following procedur
Powdered plant material was ground in a morta
for about 1 min with 10% ammonia solutiothen mixed with basic aluminiun oxide (activi
I). The mixture was packed loosely into a gla
column (20 cm long by 1.5 cm in diameter), an
the alkaloidal bases were eluted with methylen
chloride. The column was monitored by TL
(silica gel). The first 5 ml of eluate were co
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A.B . Pomilio et al . / Journal of Ethnopharmacology 65 (1999) 29–51
lected, concentrated in vacuo and then chro-
matographed (Wagner et al., 1984). DMT synthe-
sized in our laboratories, as well as harmine and
harmaline (Sigma) were used as standards.
All extracts were examined by TLC and
HPTLC, on silica gel GF254 glass-backed pre-
coated plates and CH2Cl2 –EtOH– 28% NH4OH
(85:14:1, v/v/v) as solvent and the spots werevisualized by spraying with Dragendorff’s re-
agent.
The alkaloids were also analysed in urine sam-
ples of the volunteers and controls. Test 24-h
urine specimens, including the first void of the
day, were kept in dark well-closed containers. The
samples were filtered (0.22 v) and stored at 5°C if
not immediately analysed. To 100 ml of urine
sample were added 5 N KOH (10 ml) and diethyl
ether (40 ml) with shaking in a separatory funnel.
The upper ethereal layer was filtered, dried over
anhydrous sodium sulfate and stored at −20°C
(in a freezer) until assay. The organic layer was
evaporated to dryness under vacuum at 30°C and
the residue was subjected to GC-MS. The tea
samples were processed in the same way.
2.3. Neuropsychological tests
Acute psychological and physiological effects of
Hoasca tea were assessed in human subjects.
Experienced test volunteers refer to cult-mem-
bers, who consume the tea anyway as members of these religious groups. Other volunteers refer to
Hoasca non-users, who drink the beverage for the
first time or act as controls without knowing their
role. All of them were aware of the meaning of
the experience, were drug-free and no concomi-
tant disease was present. The corresponding writ-
ten consent was obtained. Prior to the tea intake
all the subjects were evaluated in order to assess
the presence of perceptual alterations. For this
purpose the Hoffer and Osmond Test (HOD test)
(Ciprian-Ollivier et al., 1988) was taken, and theywere neuropsychologically evaluated, to check the
memory processes and visuospatial coordination.
These tests were also taken 1 h after drinking the
tea. The tests used were: Wais-R digit symbol test
(DSY), complex-figure (Ray-Osterrieth) and the
Buschke selective reminding task.
2.4. Biochemical e6aluation of the Hoasca intake
Blood samples were obtained to assess cortiso
prolactin and serotonin (5-HT) levels, at hou
0:00, 1:00 and 2:00 from taking the tea. Urin
samples were obtained at the same times in orde
to detect DMT presence.
For serum samples, the subjects need not havbeing fasting. Blood was collected by venipun
ture into plain tubes, and allowed to clot at room
temperature. After centrifugation, the serum frac
tion was separated, and stored. For the prolacti
assays the serum samples were stable for up to 2
h at 2–8°C and frozen at −20°C for up to
month, while for cortisol they were under refrige
ation for 7 days, or kept for up to 2 months a
−20°C. Prior to these assays, the samples we
allowed to come to room temperature, withou
thawing the frozen specimen by heating them in
water bath. For longer storage, if necessar
aliquots were prepared in order to avoid repeate
freezing and thawing, and stored frozen. In ou
tests fresh-prepared serum samples were use
when possible. To prevent interference in both th
prolactin and cortisol measurements, the subjec
were controlled so as not to receive any radio
pharmaceuticals for diagnostic or therapeut
purposes.
2.4.1. Serotonin
Quantitation of serotonin was performed bHPLC in the serum samples of the test volunteer
(normal range 45 – 200 ng/ml). The detailed proc
dure has been extensively described in previou
papers (Pomilio, 1995; Vitale et al., 1995). A LK
chromatograph equipped with a LKB Bromm
2249 solvent-delivery pump, a Rheodyne injecto
and a fluorometric detector Chrompack (18 nm
slit width, 1.5 s time constant) coupled to a LK
Bromma 2221 integrator (vBondapak C18, 10 vm
250 mm length×4.6 mm, i.d. column); 10 v
volume injected.
2.4.2. Prolactin
Prolactin was measured in human serum b
immunoradiometric assay-magnetic solid phas
(normal range: 2– 15 ng/ml for males and 2–2
ng/ml for premenstrual females). The Prolact
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A.B . Pomilio et al . / Journal of Ethnopharmacology 65 (1999) 29–5138
MAIA clone kit (Serono Diagnostics, USA) was
used over the range 5.0 –10 000 vlU/ml without
dilution (detection limit: 6.0 vlU/ml). This tech-
nology incorporates two high affinity monoclonal
antibodies into an immunoradiometric assay
(IRMA) system to increase sensitivity and specifi-
city compared with traditional methods (Rattle et
al., 1984). Samples, standards and controls werereacted with a mixture of monoclonal antibodies
to prolactin. The MAIA clone technique was
used not only because of its specificity and rapid
response, but also because it has the advantage
that it inhibits interference in the usual IRMA
techniques, such as endogenous factors causing
falsely elevated values. Only grossly lipemic sam-
ples had to be discarded.
For each assay, a group of tubes was prepared
in duplicate: total counts, Bo (20 vl; zero stan-
dard; absence of antigen), standards (20 vl each)
of different concentrations (40, 100, 200, 500,
2000, 5000 and 10000 vU/ml), serum (20 vl) and
control (20 vl). [125I]-prolactin reagent (40 vl)
was added to each tube, and all the tubes were
gently vortexed and sealed. All the tubes except
those of the total counts, were incubated for 1 h
at room temp. Thoroughly mixed prolactin
MAIA clone separation reagent (80 vl) was
pipetted into each tube (Bo, standards, samples
and controls) and all the tubes were gently vor-
texed. After incubation for 5 min at room temp,
the rack of tubes was subjected to magnetic sedi-mentation for 2 min and the supernatants were
carefully decanted from all the tubes. Then, di-
luted wash buffer (200 vl) was added to each
tube. After vortex-mixing each tube, and 2 min of
magnetic sedimentation, the supernatants were
carefully decanted from all the tubes, drained for
5 min and blot the tubes. Each tube was counted
for 60 s in a counter calibrated to detect 125I. A
calibration curve was run for each assay. The
mean cpm was calculated for each pair of tubes
and the mean cpm of the zero standard tubes wassubtracted from all counts to obtain the corrected
cpm.
2.4.3. Determination of cortisol
Cortisol was measured in serum samples by a125I radioimmunoassay double antibody (Diag-
nostic Products Corporation, USA) (norm
range: 5 –25 vg/dl) adequately designed for the i
vitro assessment of adrenal status. This procedur
is a competitive radioimmunoassay in which 125
labelled cortisol competes with the cortisol in th
subject sample for antibody sites. After incub
tion, separation of bound from free is achieve
by the PEG-accelerated double-antibody methodFinally, the antibody-bound fraction is precip
tated and counted. The subject sample concentra
tions are read from a calibration curve as i
conventional RIA techniques.
This test was selected due to the fact that th
antiserum is highly specific to cortisol, with ver
low crossreactivity to other compounds (e.g. na
urally occurring steroids or therapeutic drug
that might be present in human samples. How
ever, volunteers undergoing therapy with pred
nisolone were discarded due to the 37% observe
crossreactivity with prednisolone and/or pred
nisone (prednisone is converted to prednisolon
in vivo). Neither protein, lipemia, bilirub
(severe icterus), nor hemolysis have any effect o
the assay. Only EDTA should be avoided a
anticoagulant because it causes significant devia
tions of the measured cortisol level from th
determined when serum is used. The accuracy o
the assay has been further verified in patien
comparison studies against two commercial
available cortisol radioimmunoassays.
All components were at room temp prior tuse. The tubes were labeled in duplicate: T (tota
counts), NSB (nonspecific binding; 10 vl of zer
standard A), A (zero standard; maximum bind
ing; 10 vl), and B through F (human serum
standards containing values of cortisol 1, 5, 1
20 and 50 vg/dl, equivalent to 27.6, 138, 276, 55
and 1380 nmol/l, respectively; 25 vl each), serum
samples (25 vl each) and controls (25 vl). [125I
cortisol (40 vl) was added to the T and NS
tubes only and tubes T were counted. [125I]-cort
sol and cortisol antiserum (40 vl each) was addeto all the tubes, except the T and NSB tube
vortexed and incubated for 45 min at 37°C in
water bath. Thereafter the cold precipitating solu
tion (400 vl; goat anti-rabbit k-globulin and d
lute PEG in saline) was added to all tube
vortexed and incubated for 5 min at room tem
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A.B . Pomilio et al . / Journal of Ethnopharmacology 65 (1999) 29–51
perature. After centrifugation for 15 min at
3000× g , the supernatants were decanted and the
respective precipitates were retained for counting.
Each tube was counted for 1 min. First, for each
pair of tubes the average NSB-corrected cpm was
calculated: net counts=average cpm−average
NSB cpm. Then, the binding of each pair of tubes
was determined as a percent of maximum binding(MB), with the NSB-corrected counts of the A
tubes taken as 100%. The tracer has a high spe-
cific activity, with total counts of ca. 70000 cpm
at iodination. Maximum binding is about 40–
60%. The detection limit is about 0.3 vg/dl. Corti-
sol concentrations for the human volunteers were
estimated by interpolation from the calibration
curve.
2.5. GC -MS analysis
A 24-h urinary sample was collected without
any additives, kept refrigerated during collection.
The total volume (in ml) was recorded. Aliquots
could be stored under refrigeration at 2–8°C for
up to 7 days, or for up to 1 month frozen at
−20°C. Analyses of the composition of each
plant extract, liana B . caapi and the leaves of
P. 6iridis, and the composition of Hoasca teas
were performed by GC-MS. Components of
the urine samples of control and test subjects
(Hoasca probandi), as well as those of psychoticpatients were also analysed, and matched with
controls. Urine samples were taken prior to and
2 h after the administration per-os of ca. 100 ml
of Ayahoasca, prepared by the members of
the UDV of Brazil. A VG TRIO-2 Mass Lab
apparatus with helium carrier gas was used to
perform GC-MS. Split: 100:1. Column pres-
sure: 10 psi. Data were processed by the Lab
Base GC- MS data system. Mass scanning was
performed in the range 30–800 for each peak
sample. A SPB-1, 30 m length×0.20 mm i.d.,fused-silica capillary column was used with the
following temperature programm: 60°C for 1 min,
60– 290°C (10°C/min) and 5 min at 290°C. An
aliquot of the organic extract, containing total
alkaloids, was directly injected for GC-MS analy-
sis.
3. Results and discussion
The results involved in this paper refer to diffe
ent topics related to the knowledge of the Aya
hoasca beverage or Hoasca tea, whose use
increasing worldwide especially due to its implica
tion in religious cults. The first feature that ha
been considered in this paper refers to the ethnobotany and the ethnochemistry, the source-plan
used and preparation and intake of the Hoasc
tea context. The second is related to the chemica
constituents involved, not only in the tea but als
in the botanical species used to prepare it. Th
third refers to the neuroendocrine biochemic
contribution, and the fourth is the neuropsycho
logic parameters. We were interested in the analy
sis of the short-lasting changes in perceptio
cognition and thought accompanying other ps
chological functions in consumers of Hoasca te
and comparison with psychotic subjects. Neithe
moral nor religious criticism was involved at al
3.1. Ethnobotany and ethnochemistry of Hoasca
tea
The use of Ayahoasca or Hoasca tea in thes
syncretic cults resembles the recreational aborig
nal use, where visions and hallucinations play
very important role, and the members obtain
after the intake, a pleasant feeling of satisfaction
freedom, and alleviation of some physical anmental problems. The outstanding difference
that in the cults the Hoasca intake has a sacra
mental connotation immersed in a religious con
text of ethical behaviour, fraternity and respe
towards other people as expected from a religion
Consequently, the Ayahoasca practice for rel
gious purposes is allowed by the Brazilian Gov
ernment owing to the psychological, social an
moral profits obtained from cult-membership
Furthermore, the members belong to the middle
class and usually are politicians, executives anoutstanding professionals, particularly physician
who consume it regularly as a sacrament at ce
tain times during the cult services, in the grou
(‘nucleo’) to which they belong, under the superv
sion of a ‘mestre’ (leader, like a priest), who ha
learned during months or years the correspondin
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A.B . Pomilio et al . / Journal of Ethnopharmacology 65 (1999) 29–5140
intellectual, religious and hallucinogenic-plant
knowledge. Some cult-members have consumed
Hoasca for over 30 years without apparent ad-
verse health effects. On the contrary, some of
them report cures of physical and mental diseases.
This Ayahoasca cult-drink is usually prepared
from B . caapi and Psychotria species as the only
admixture, particularly the leaves of P.6
iridis orrelated species (P. carthagenensis or P. leiocarpa).
The most common is P. 6iridis, which seems to
produce more intense hallucinations than P.
carthagenensis, while P. leiocarpa is similar to the
first in its effects (Aranha et al., 1991). The UDV
recognizes two growth forms (‘tutunaka’ and
‘kaupuri’) of B . caapi (‘mariri’), each giving ap-
parently different kinds of Hoasca tea. Likewise,
different species of Psychotria used as admixtures
result in a different effect of this drink.
The Ayahoasca beverage is usually prepared by
the cult-people (mestre or acolysts) of each group,
similar to the Ayahuasqueros. According to our
results, the composition of the tea varied little
from one to another close-related group, although
relative differences were quoted. Preparation con-
sists of packing layers of vine B . caapi alternately
with leaves of Psychotria sp. in a vessel, water is
added and the mixture is boiled in a similar way
to previous detailed reports of Rivier and Lind-
gren (1972). When cold, the decoction is ready for
consumption. There are long-time and short-time
preparations of the decoctions, the former withaddition of fresh water kept boiling. Some people
in Brazil, not belonging to the groups that we
contacted, used to swallow Ayahoasca (Lewis and
Elvin-Lewis, 1977) kept in bottles as previously
reported (see Section 2), and also in vessels similar
to those used in Paraguay, Argentina and
Uruguay for drinking the ‘mate’ infusion pre-
pared with the non-hallucinogenic plant (called
‘yerba mate’, Ilex paraguayensis).
The members meet in cult-services, where
Hoasca tea is drunk, the amount differing accord-ing to its concentration is controlled by the
mestres, usually ca. 100– 150 ml. Some of them
spit and vomit, which is considered a soul purifi-
cation, and immediately thereafter the visions be-
gin. The mestre guides the visions and helps the
beginners in order not to have a bad experience.
The cult-members go to their work the followin
day, showing normal behaviour without visib
signs of hallucinogen consumption. Apparent
no addiction is detected. This practice resemble
to a certain extent that reported previously in th
Acre territory of Brazil (Prance, 1970; Prance an
Prance, 1970), except for the whole religious con
text. Ayahoasca results in a well-controlled hallucinogenic state when compared with parenter
DMT.
Subject descriptions of the effects of Ayahoasc
is related to the vision of unknown places, conta
with absent or dead people, animals, valuab
objects, and usually traditional or new person
aspirations. But the main characteristic is th
creation of great suggestibility. Personal exper
ences have been previously reported in deta
(Schultes, 1968; Rivier and Lindgren, 1972). Th
effects of the Hoasca teas that we have analyseappeared at least ca. 40 min after intake, some
times later, and lasted for about 2 h, dependin
on the dose and on the individual variations,
sometimes being prolonged by taking more te
every hour. Likewise, neuroendocrine paramete
suffered variations too (vide infra). Shortly afte
intake vegetative symptoms appear, such as tin
gling sensation, trembling, nausea, sometimes my
driasis, elevation of the blood pressure and a
increase in the pulse rate, which disappear wit
the first visions. Optical illusions, pseudohallucnations and later real hallucinations, appear. A
first a shining coloured veil appeared between th
subject and their surroundings, and thereafter, th
vision of coloured objects, geometrical vision
accompanied by a feeling of harmony and a desir
to laugh and communicate with the other mem
bers. After the symptoms disappeared, they wer
able to describe what had happened. The vision
and sensations diminished but the harmony an
the spiritual lucidity remained. Furthermore, th
contact with the other Hoasca drinkers appeareto remain even the day after. A light pleasan
fatigue followed and there were no side-effect
These personal experiences closely resemble thos
reported by Rivier and the anthropologist Ru
when living with the Culina Peruvian Amazo
Indians (Rivier and Lindgren, 1972; Ruf, 1972)
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A.B . Pomilio et al . / Journal of Ethnopharmacology 65 (1999) 29–51 4
All cases tested in this paper reported similar
good experiences, without bad sensations and/or
feelings of anguish such as those caused by the
hallucinogenic drink (shuri fisopa tukondi, black
Ayahuasca) prepared with B . caapi , P. 6iridis and
leaves of Lygodium 6enustum Sw. (Schizaeceae) of
the Sharanahua Peruvian Amazon Indians (Rivier
and Lindgren, 1972), or reported by Rodrıguezand West with the yaje potion without visions,
used by the witch tribe-man for medicinal pur-
poses (Rodrıguez et al., 1982).
3.2. Chemical composition of the plant material
and the Hoasca teas
The plant material used for the preparation of
each Hoasca tea, which we received from Brazil,
was identified by the botanists, who always re-
ported that the liane samples were those of B .
caapi , and the leaves corresponded to P. 6iridis.
Knowing that cultivars of B . caapi have been
reported (Rivier and Lindgren, 1972; McKenna et
al., 1984; Hegnauer, 1990) as well as different
species of Psychotria and kinds of P. 6iridis, and
that Hoasca may be prepared from different
‘kinds’ of B . caapi and Psychotria species, we
especially insisted in this matter, however the
botanists found no significant morphological dif-
ferences in the samples. Only the alkaloids were
studied in the plant materials and the drinks.
Concerning the Hoasca teas, all samples studiedin this paper showed that different batches from
the same cult-group were generally similar, while
a variation particularly in the relative composition
of the harmane alkaloids was observed from dif-
ferent cult-groups. Consequently, we present here
the two types of Hoasca that we detected, indicat-
ing the average alkaloid composition.
Hoasca tea type 1 contained, on average,
0.065% w/v total alkaloids, tR 15.72 min DMT
(14.1%, 9.1 mg/100 ml), 19.70 min THH (6.5%,
4.2 mg/100 ml), 19.83 min N -Me-THH (6.3%, 4.1mg/100 ml), 20.23 min harmaline (traces, B0.1%)
and 20.47 min harmine (73.1%, 47.5 mg/100 ml)
(tR refer to GC-MS). An example of tea type 1 is
shown in Fig. 1. The other typical Hoasca tea
type 2, on average contained, 0.070% w/v total
alkaloids, tR 15.73 min DMT (12.5%, 8.8 mg/100
ml), 19.65 min THH (37.8%, 26.5 mg/100 ml
19.80 min N -Me-THH (36.4%, 25.5 mg/100 ml
and 20.58 min harmine (13.2.1%, 9.2 mg/100 ml
An example of tea type 2 is shown in Fig. 1 Bot
types are different from previous Ayahuasca com
positions reported (Rivier and Lindgren, 197
McKenna et al., 1984). Although both types seem
to be quite different several chemical propertiare common, such as: the relationship of harman
alkaloids to DMT (6.5:1 and 7:1, respectively), th
concentration of DMT (8.5– 9.5 mg/100 ml; c
0.5 mM), and the total alkaloids (65–70 mg/10
ml) are all practically the same in both tea type
and furthermore, harmaline is not present or on
detected in trace amounts in both cases. The mai
difference is the relative composition of the ha
mane alkaloids, THH:N -Me-THH:harmine bein
ca. 1:1:12 in type 1 tea and 3:3:1 in type 2. Th
differences could be related to different B . caap
cultivars employed to prepare the drinks, or to th
method of preparation. In fact, the variable alka
loid composition in leaves and stems of B . caap
may be due to the presence of alkaloid
chemodems (Hegnauer, 1990), e.g. local chemic
populations. Environmental variations (soil, expo
sure to sunlight and so on) can not be discarded
However, in this study the relative composition
of the alkaloids identified in the plants receive
from Brazil used for the preparation of the drink
differed from those of the drinks. The leaves of P
6iridis contained on average 0.19–0.35% total akaloids relative to dry weight, DMT (tR 15.7
min) being the main component in all cases, alon
with traces of DMT N -oxide (tR 16.57 min) an
MTHC (tR 17.30 min). No MMT was found i
any of the samples of P. 6iridis. Fig. 1 is shown a
an example of the leaves of P. 6iridis. In averag
the stems of B . caapi contained 0.18% total alka
loids relative to dry wt, of which 97% wa
harmine (tR 20.50 min) and 1% was THH (t
19.70 min). Some stems contained only harmin
and traces or none of THH. Neither harmalinharmol nor methoxytryptamines were detected i
the samples of B . caapi (Fig. 1).
The GC-MS were analysed, and the mass frag
mentograms of the alkaloidal extracts of B . caap
samples, P. 6iridis samples and beverages we
monitored for the occurrence of traces of th
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A.B . Pomilio et al . / Journal of Ethnopharmacology 65 (1999) 29–5142
Fig. 1. Examples of GC-MS of Hoasca tea, leaves of P. 6iridis, stems of B . caapi , Probandi and patients.
known indoleamines and i-carbolines focussing
on the respective mass numbers of the base peaks
and molecular ions. The mass fragmentation was
in agreement with previous reports (Holmstedt
and Lindgren, 1967; Rivier and Lindgren, 1972).
Concerning tryptamines, in these samples only
DMT was obtained, along with its N -oxide.DMT: 30, 42, 58 (bp), 77, 103, 130, 188 (M)
(Holmstedt and Lindgren, 1967). DMT N -oxide:
58 (bp), 103, 115, 130, 143, 188, 204 (M). MTHC
(2-methyl-1,2,3,4-tetrahydro-i-carboline): 78,
102, 115, 143 (bp), 186 (M) (Agurell et al., 1969;
Rivier and Lindgren, 1972). Harmine (1-methyl-7-
methoxy-i-carboline): 44, 63, 75, 106, 169, 21
(bp and M) (Holmstedt and Lindgren, 1967
Harmaline (1-methyl-7-methoxy-3,4-dihydro-i
carboline): 169, 170, 186, 198, 199, 212, 213, 21
(bp and M) (Rivier and Lindgren, 1972). THH
(1-methyl-7-methoxy-1,2,3,4-tetrahydro-i-carbo-
line): 43, 44, 57, 91, 158, 172, 201 (bp), 216 (M(Holmstedt and Lindgren, 1967). N -Me-THH
(1,2-dimethyl-7-methoxy-1,2,3,4-tetrahydro-i-ca
boline): 43, 44, 57, 85, 172, 201, 215 (bp), 23
(M).
The i-carbolines and DMT concentration
present in the two types of Hoasca teas are diffe
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A.B . Pomilio et al . / Journal of Ethnopharmacology 65 (1999) 29–51 4
ent from those previously reported from the Peru-
vian Amazon (Rivier and Lindgren, 1972;
McKenna et al., 1984) and are nearly intermedi-
ate. However, in the case of these hallucinogenic
drinks what is important is the relative concentra-
tion of harmane alkaloids and DMT, and the
corresponding harmane levels to cause MAO inhi-
bition. The amounts of i-carbolines in the typicaldose of these two types of Hoasca teas are well
below the threshold at which they are hallucino-
gens themselves (ca. 300 –500 mg for harmaline
and THH; ca. 1000 mg for harmine, and 400 mg
for physical symptoms (Pennes and Hoch, 1957;
Naranjo, 1967)), but well within the range for
acting as highly selective inhibitors of MAO-A,
the form for which serotonin, and other
tryptamines (e.g. DMT) are the preferred sub-
strates (Yasuhara et al., 1972). In vitro, i-carboli-
nes are MAO inhibitors at ca. 10 mM (Buckholtz
and Boggan, 1977; McKenna et al., 1984) which is
2 to 3 orders of magnitude lower than the hallu-
cinogenically active dose. Nevertheless, greater
amounts of i-carbolines than those detected here
would be necessary for their hallucinogenic effect,
owing to the non-synergistic i-carbolines mecha-
nism (McKenna et al., 1984). In spite of the low
DMT levels obtained here they are still well
within its activity range, which is lower than i.m.
(Szara, 1956) or i.v. (Strassman, 1994; Strassman
and Qualls, 1994; Strassman et al., 1994) DMT
threshold under conditions of MAO inhibition.This selectivity of i-carbolines for MAO-A
over MAO-B, combined with their relatively low
affinity for liver MAO compared to brain MAO,
may explain why there are no risk of hypertensive
crises post-ingestion of Ayahuasca, particularly in
subjects who consume tyramine-containing foods
(Yasuhara et al., 1972). Urine samples were
analysed by GC-MS (Vitale et al., 1995), showing
four groups according to DMT response. First, all
controls were free from DMT. Second, all sub-
jects (new and common users) showed the pres-ence of DMT in the urine post Ayahoasca, which
was possitively correlated with the perceptual al-
terations. Third, prior to the tea intake, DMT was
detected only in the urine samples of usual con-
sumers of Ayahoasca. Finally, urine samples from
drug-free acute schizophrenic patients showed
DMT occurrence. A GC-MS example of a pos
tive-DMT subject urine after Hoasca intake
given in Fig. 1 (tR 10.25 min: caffeine; 11.98 mi
urea; 15.73 min DMT). Further, an example o
the urine analysis of an acute schizophren
patient, who had not taken Hoasca tea is als
given in Fig. 1 (tR 15.53 min DMT; 17.42 m
acridine derivative; 21.20 min sitosterol; 23.22 micholesterol; 23.87 min stigmasta-3,5-dien-7-on
the three latter peaks probably from dietar
origin).
3.3. Neuroendocrine measurements
Blood samples were assayed for serotonin, pro
lactin and cortisol prior to and after ingestion o
Hoasca in order to obtain information about th
serotonergic response to Hoasca.
As is known, cortisol is the major glucocort
coid secreted by the adrenal cortex, and is physio
logically effective in anti-inflamatory and bloo
pressure maintenance, and is also involved i
gluconeogenesis, calcium adsorption and the s
cretion of gastric acid and pepsin. Measuremen
of blood cortisol levels is especially useful as a
indicator of adrenocortical function. Circulatin
cortisol is usually determined using stimulatio
and suppression tests, such as ACTH stimulation
ACTH reserve (metyrapone suppression) and dex
amethasone suppression, which provide suppor
ive information on adrenocortical functioHowever, anomalous cortisol concentrations wer
obtained in patients with acute infection, seve
pain, diabetes mellitus, heart failure and i
women, either pregnant or on estrogen therapy, a
well as in certain virilizing syndromes and iatro
genic conditions which raise other natural steroid
to unphysiologic high concentrations. Therefor
in this study we used the highly specific doub
antibody radioimmunoassay (detection lim
about 0.3 vg/dl) to prevent the interferences ob
served with less specific antisera used in othRIA procedures (Diagnostic Products Corpor
tion, 1985).
Human prolactin is a hormone secreted by th
anterior pituitary gland under the direct contr
of the hypothalamus, the thyrotrophin releasin
hormone (TRH) being known to have a stimula
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A.B . Pomilio et al . / Journal of Ethnopharmacology 65 (1999) 29–5144
Fig. 2. Ayahoasca effects: 5-HT serum levels. Fig. 4. Ayahoasca effects: serum cortisol levels.
tory effect upon prolactin secretion. A lot of
known physiological states are associated with
hyperprolactinemia, therefore, we performed the
measurement of prolactin in serum as an index of
functional disorder within the hypothalamic pitu-
itary axis.
Results of serotonin, prolactin and cortisol lev-els are shown in Figs. 2–4, respectively.
Sequential measures of prolactin and cortisol
showed significant responses in blood levels nearly
1 h after Ayahoasca intake in agreement with the
beginning of the hallucinogenic effect, and the
subjects could be grouped accordingly. One group
of Hoasca new consumers showed increasing neu-
roendocrine response, which correlated with a
pronounced perceptual response, and in agree-
ment with previous dose-dependent studies with
synthetic DMT and other hallucinogens (Prescott
et al., 1984; Tuomisto and Mannisto, 1985; Van
der Karr et al., 1989; Strassman, 1994; Strassma
and Qualls, 1994; Strassman et al., 1994), such a
lysergic acid diethylamide (LSD), which hav
been shown to act mainly via serotonin 5-HT
receptors, although the exact mechanism of the
action is still unknown. Pupil diameter, mea
arterial blood pressure, pulse, and core temperature also rose dose-dependently.
Neuroendocrine blood levels and heart rate re
sponses demonstrated significant reduction
across administrations, suggesting tolerance (se
ond grouping), similar to DMT administration
Although the lack of psychological tolerance sup
ported a role for DMT in natural-occurring psy
choses (Strassman, 1994; Strassman et al., 1994
The third group showed, instead, a continue
rise in both cortisol and prolactin, along with
decrease in serotonin. In all cases the respon
was short in time, but could be maintained with
second intake 1 h after the first drink. The thre
groups evidenced expected different perceptual e
fects with values in agreement with the individu
biochemical responses, indicating that psychedel
effects may be required to perturb biological e
fects. All these effects may be mediated by 5-HT
2A, 5-HT-2C, or 5-HT-1A subtype activation, a
in the case of DMT (Strassman, 1994; Strassma
et al., 1994).
The determination of the receptor subtype ac
counting for the effects of psychedelic compoundis hampered by the fact that 5-HT-2 recepto
belong to a family of pharmacologically an
structurally closely related receptors: 5-HT2,
HT1C and the recently cloned 5-HT2F. It ha
been proposed to re-name these receptors as
HT2A, 5-HT2C and 5-HT2B, respectively. IFig. 3. Ayahoasca effects: serum prolactin levels.
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A.B . Pomilio et al . / Journal of Ethnopharmacology 65 (1999) 29–51 4
contrast with the rat brain, in the human brain it
has not been possible until now to visualize the
mRNA’s coding for the 5-HT2A and the 5-HT2C
receptors. The pharmacological characteristics of
5-HT2A and 5-HT2C receptors differ among spe-
cies, and there are also differences in 5-HT2C
receptors distribution in the human brain as com-
pared to the rat brain. The human anatomicalstudies on the distribution of serotonin receptors
suggest that the possible targets for the action of
hallucinogenic drugs is widespread, and could be
associated with neocortical, limbic and also with
mechanisms mediated through the basal ganglia
in the human brain (Palacios et al., 1994).
3.4. Neuropsychological parameters
Results from the HOD test and neuropsycho-
logical evaluation are shown in Figs. 5 and 6.
Once the beverage was taken by the subjects,
no effects were reported up to 35 min after intake,
at this moment one group of subjects reported
marked perceptual alterations in the sense of dis-
tortion of true perceptions, mainly visual. No
auditory hallucinations were reported at any time
by the subjects. Meanwhile two groups of subjects
experienced strong perceptual alterations, as
shown in Fig. 5, the other only reported slight
time– space disorientation. All of them experi-
enced changes in mood, with unmotivated laugh-
ing. The effect on neuropsychological tasks was
Fig. 6. Ayahoasca effects: neuropsychological parameters.
significative (Fig. 6). The comparison of the r
sults shows that Ayahoasca had slight effects o
attention and memory processes and stronger efects on visuospatial construction. The Wais-
digit symbol test (DSY) decreased significative
after the tea, meaning interference with sustaine
attention. The Buschke selective reminding tas
showed a decrease in consistent long term r
trieval (CLTR) but not significative changes i
long term storage (LTS), long term retriev
(LTR) and total recall (TR). Visuoperceptual pro
cesses were significatively affected, as shown b
the results of the complex-figure (Ray-Osterrieth
The perceptual distortions are primarily visuin nature, light flashes, colours, abstract form
and figures, illusions, primarily geometrical pa
terns, moving very fast, having sometimes ver
deep emotional content and connotation. There
an inability to keep attention focused on an
outside event. There is an enhanced dependenc
on the environment for structure and for symbol
meanings, and increased association. It is ou
standing the rapid onset and the short-lastin
effect.
4. Conclusions
GC-MS analysis of samples of Ayahoasca bev
erage and plant material, showed the presence o
i-carbolines and DMT, leading mainly to twFig. 5. Ayahoasca perceptual effects.
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A.B . Pomilio et al . / Journal of Ethnopharmacology 65 (1999) 29–5146
types of tea according to the quantitative re-
sults. Moreover, urine samples of psychotic
unmedicated patients also gave DMT resembling
those of the Ayahoasca new and usual con-
sumers. In Ayahoasca i-carbolines as strong
MAO inhibitors prevent DMT from being de-
stroyed by liver MAO in the first pass effect.
Therefore, DMT reaches and crosses the BBB,exerting 5-HT2 agonist effects on the CNS. This
5-HT2 agonism accounts for the biological and
behavioural disturbances induced by the tea
(Eison, 1994). The biochemical profile of volun-
teers under the effects of Ayahoasca was stud-
ied. Neuroendocrine and neuropsychological
data before and after Hoasca intake were deter-
mined to assess differences between Hoasca
drinkers and controls.
Decreased MAO kinetics have been previously
reported in schizophrenia by several authors(Davis et al., 1982). It is assumed that this phe-
nomenon may be the basis for the non destruc-
tion and consequent accumulation of methylated
indolealkylamines, such as DMT, in these pa-
tients. Our previous papers on the subject were
always related to the occurrence of this com-
pound in urine from psychiatric patients and the
level of perceptual alterations (Ciprian-Ollivier
et al., 1986; Ciprian-Ollivier, 1991). This is also
shown in this report on Ayahoasca owing to the
strong effects on perception (see neuropsycho-logical results).
Furthermore, the neuropsychological findings
support that Ayahoasca affects more visuospa-
tial functions, due to subtle perceptual interfer-
ence, than cognitive processes. In this study this
was confirmed by the HOD test results, which
clearly recorded perceptual alterations in all
three groups of subjects.
Biological parameters led us to think about a
serotonergic agonism, mainly over 5-HT2 recep-
tors. These receptors have been involved in aregulatory effect on synthesis and release of DA,
and also explain the rise in prolactin levels
(Heym and Jacobs, 1987; Iqbal et al., 1991; Lin-
denmayer, 1992). Serotonin has also a regula-
tory effect on hypothalamic cortisol regulation,
in a way that 5-HT2 receptors agonism can
raise cortisol levels. Both, at least, in first-tim
consumers.
Recently, and especially in the last few year
interest was focused on serotonergic mechanism
in psychoses pathogenesis in relation to th
mechanism of action of the so called ‘atypic
antipsychotics’ (Muller-Spahn, 1992; Wong
al., 1994). However, the ‘transmethylation hypothesis of schizophrenia’ proposed this partic
pation more than 35 years ago (Wyatt an
Gillin, 1976) but received little attention. Thu
clozapine, risperidone, ritanserine (Davis et a
1991) show a mechanism of action, which als
involves the ability to interact with several 5-H
receptors (Nelson et al., 1994; Kuccharewicz
al., 1994; Strassman, 1994; Strassman an
Qualls, 1994; Strassman et al., 1994), the mo
important being 5-HT2. Actually, DMT inte
acts with this receptor. We can hypothesize tha
part of the antipsychotic effect may be relate
to blocking DMT activity on this receptor b
the new antipsychotics (Aghajanian and Marek
1994; Ciccocioppo et al., 1994; Costall and Nay
lor, 1994; Donetti et al., 1994; Johnson et a
1994).
On the other hand, strong relationships b
tween 5-HT and DA neuron activity was r
ported (Steward et al., 1994). In summary, th
in vivo study represents an additional step to
wards understanding the psychopharmacology o
Ayahoasca and further confirms that Ayahoascrepresents an experimental psychosis with com
mon features with the transmethylation hypothe
sis of schizophrenia, encouraging furth
research.
Acknowledgements
Thanks are due to CONICET (Argentin
and Universidad de Buenos Aires (UBA, A
gentina) for financial support, to LANAISEMAR (CONICET) for GC-MS facilities an
to Professor Dr Ramon A. Palacios and Dr En
rique M. Zallocchi (Laboratorio de Plantas Va
culares, Departamento de Ciencias Biologica
FCEN, UBA) for the identification of the plan
material. We are especially grateful to the Pres
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A.B . Pomilio et al . / Journal of Ethnopharmacology 65 (1999) 29–51 4
dent of the Scientific Studies Society of the Uniao
do Vegetal (‘Santo Daime’, Brazil), and the cult-
members for the interest in our research and their
helpful assistance.
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